title: 3D presentation of a neurotrophic factor for the regulation of neural progenitor cells.
abstract: BACKGROUND
  Adequate cell-scaffold interactions and neurotrophin support are essential factors for neural regeneration.
  
  
  OBJECTIVE
  To provide insight into the biofunctionalization of complex 3D scaffolds with nanoscale precision, as well as the effect of spatial distribution of brain-derived neurotrophic factor (BDNF) and its prolonged stimulation in combination with enhanced cell affinity of nanofibrous scaffolds on the survival/proliferation and neurite outgrowth.
  
  
  METHODS
  We developed a versatile approach using layer-by-layer self-assembly to incorporate cell adhesion and spatial representation of neurotrophic factors into complex nanofibrous scaffolds.
  
  
  RESULTS
  Heparin/poly-L-lysine (PLL) polyelectrolyte multilayers (PEMs) were deposited on electrospun poly-ε-caprolatone nanofibers. Well-controlled amounts of BDNF were immobilized on the PEM-modified nanofibers. In addition, longer neurite outgrowth was observed in neural progenitor cells cultured on PLL-terminating PEM scaffolds. The immobilized BDNF on PLL-terminated PEM scaffolds resulted in significantly longer neurites and higher cell numbers (p < 0.01) compared with BDNF-free and BDNF-adsorbed PLL-terminating scaffolds. Interestingly, there was no upregulation of TrkB-FL, TrkB-T1 or GAP-43 mRNAs with immobilized BDNF in day 5 cultures.
  
  
  CONCLUSIONS
  This work reinforces the importance of the combinatorial effects of biomaterial scaffold nanostructure and spatial presentation of neurotrophins in directing neural progenitor cell fates.
authors.affiliation: Department of Materials Engineering, Monash University, VIC 3800, Australia.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhou
authors.forename: George
authors.initials: G
authors.lastname: Thouas
authors.forename: Claude
authors.initials: C
authors.lastname: Bernard
authors.forename: John S
authors.initials: JS
authors.lastname: Forsythe
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004573:Electrolytes / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D011091:Polyesters / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004573:Electrolytes; D055767:Immobilized Proteins; D011091:Polyesters; C016240:polycaprolactone; D011107:Polylysine; D006493:Heparin
keywords: brain-derived neurotrophic factor; immobilization; layer-by-layer; neural tissue engineering; polyelectolyte; self-assembly nanofiber